Effects of nucleobase metalation on frontier molecular orbitals: potential implications for pi-stacking interactions with tryptophan.
Biochemical recognition processes mediated through pi-stacking interactions are a potential target for rational drug synthesis. A combination of electrostatic, hydrophobic, solvation, charge-transfer, induction, and dispersion interactions has been used to account for the three-dimensional arrangements observed in such motifs. A principal example involves the interaction of purine and pyrimidine rings of nucleic acids with aromatic amino-acid residues such as tryptophan, phenylalanine, and tyrosine. Protonation, alkylation, or coordination of a metal ion such as Pd(II) or Pt(II) to a nucleobase strengthens this interaction by lowering the energy of the lowest unoccupied molecular orbital (LUMO) of the modified nucleobase and improving overlap with the highest occupied molecular orbital (HOMO) in N-acetyl tryptophan. The relative energy difference between the frontier orbitals of isolated molecules, obtained using Density Functional Theory (DFT), is explored as a predictive tool for the strength of the pi-stacking interaction of the nucleobase/tryptophan pair. From the optimized structures of these species, evaluation of the donor-acceptor HOMO-LUMO gap (Deltaepsilon d-->a) suggests that this parameter is a promising predictor of pi-stacking strength for the donor-acceptor pairs presented in this study. The analysis correlates well with experimental association constants, measured by fluorescence spectroscopy, of metallated and alkylated nucleobases with tryptophan in comparison to free nucleobases.
Anzellotti
Atilio I
AI
Department of Chemistry, Virginia Commonwealth University, Richmond, Virginia 23284-2006, USA.
Bayse
Craig A
CA
Farrell
Nicholas P
NP
D003596:Cytosine / Q000031:analogs & derivatives* / Q000737:chemistry; D006147:Guanine / Q000031:analogs & derivatives* / Q000737:chemistry; D008956:Models, Chemical; D008958:Models, Molecular; D009942:Organometallic Compounds; D009944:Organoplatinum Compounds / Q000737:chemistry; D010165:Palladium / Q000737:chemistry; D010984:Platinum / Q000737:chemistry; D055672:Static Electricity; D013816:Thermodynamics; D014364:Tryptophan / Q000031:analogs & derivatives / Q000737:chemistry*
D009942:Organometallic Compounds; D009944:Organoplatinum Compounds; D010984:Platinum; D010165:Palladium; D006147:Guanine; D014364:Tryptophan; D003596:Cytosine